Cardiovascular diseases are currently the leading cause of death in developed countries, and represent a growing financial burden on health care. Atherosclerosis, the narrowing of major arteries by fatty plaques, constitutes the single most important contributor to this group of diseases. However, in over half of affected individuals, the condition is left undetected and the earliest clinical manifestations are myocardial infarction, stroke, or sudden death. In particular, carotid artery stenosis (carotid artery disease—CAD), is responsible for approximately half of ischemic strokes, and is mostly caused by carotid atherosclerosis.
Landmark clinical trials over the past two decades have demonstrated that surgical intervention in cases of symptomatic high-grade stenosis can reduce the risk of subsequent stroke (Barnett et al, 1998; Ferguson et al 1999; Gillard, 2003). However, it has also been shown that the degree of stenosis is not predictive of risk for stroke; it is rather the presence of unstable, inflamed atherosclerotic plaques that is a more accurate predictor of impending stroke. Therefore, screening patients diagnosed with CAD for carotid atherosclerosis is recommended; however, such screening (MRI or X-ray angiography) might be costly.
Surgical treatment for CAD is performed via a procedure called endarterectomy, which typically comprises surgical removal of plaques from the artery, but unfortunately carries a high mortality risk of 2-10%. To justify such a high mortality risk and qualify patients for high-risk endarcterectomy, it is necessary to more accurately diagnose CAD caused by unstable atherosclerotic plaques, which are predictive of stroke.
Most patients with ischemic stroke or transient ischemic attack are screened for internal carotid artery stenosis. The current standard of care for detecting carotid stenosis is based on conventional imaging techniques such as ultrasound and angiography. These methods provide information about the structural consequences of CAD, such as luminal stenosis, but yield little to no information about plaque development and plaque characteristics within the vessel wall. None of these imaging techniques is able to provide information on the molecular or cellular events within the plaque that predispose it to rupture (i.e., an unstable plaque), and hence predict the real risk for stroke.
X-ray angiography remains the current gold standard imaging technique; however, it has many limitations. Angiography simply images the lumen of the vessel, and fails to detect atherosclerotic lesions that do not protrude into the lumen and provides little information on atherosclerotic plaque composition. Thus, it cannot differentiate between unstable and stable plaques and, therefore, is unable to predict the risk of plaque rupture. Consequently, because it is mostly symptom-driven, its main value is in delineating the causative lesion in a symptomatic patient. However, because of positive remodelling, a ‘normal’ angiogram cannot be interpreted as indicating an absence of atherosclerosis. Moreover, MRI and x-ray angiography screenings are costly.
Therefore, there remains a need in the art for a cost-effective method of screening atherosclerotic plaques to identify unstable plaques and more accurately predict the risk of rupture for heart attack and stroke.